The proposed MIDARP Program is envisioned to be the vehicle by which biomedical research in the substance abuse arena is initiated on the campus of Hampton University. The underlying goal of the program is the unbridled development of a vigorous and sustainable biomedical research program on substance abuse. This goal will be realized via a series of planned activities that are designed to enhance the research culture by augmenting the biomedical research infrastructure, by creating faculty development programs that facilitate the training of minority faculty members and foster interdisciplinary collaboration between the School of Pharmacy and the Departments of Biology, Chemistry and Psychology and to facilitate the training of graduate and undergraduate minority students in the biomedical sciences, particularly in substance abuse research. Furthermore, the proposal seeks to elucidate the underlying biochemical mechanisms associated with the neurotoxicity occasioned by 3,4-methylenedioxy-methamphetamine ("Ecstasy," MDMA). Toward this end, five research projects have been proposed: 1. Synthesis of potential metabolites and antagonists of MDMA. 2. Induction of apoptosis in neuritic cells innervated by serotonergic and dopaminergic neurons, by metabolites of MDMA. 3. In Vitro study of the metabolism of MDMA using human hepatocytes 4. Interactions between MDMA metabolites and dopamine and serotonin transporters. 5. The impact of MDMA metabolites on a variety of brain regions and processes in rats. It is anticipated that the results garnered from the planned activities will significantly enhance the existing body of knowledge on the mechanisms involved in the deleterious effects of MDMA.